In the U.S., approximately 45 million individuals have osteoporosis or low bone mass, and an estimated 1.5 million osteoporotic fractures occur annually. Women bear a disproportionate burden of the costs and consequences of fracture, in part because the hormonal changes around menopause heighten fracture risk. Combined oral contraceptives (OCs), the leading method of contraception in the U.S. and worldwide, may currently represent the most common hormonal exogenous exposure for U.S. women. Use among women in their later reproductive years may be increasing due to recent changes in recommendations. While emerging evidence suggests benefits to bone mass from perimenopausal OC use, the effects on fracture of present-day OC formulations are unknown. A recent report from the World Health Organization notes this as a key evidence gap regarding the benefits and risks of OC use. We propose a population-based case-control study to evaluate whether OC use during later reproductive years (age >40 years ) is associated with the risk of fractures occurring around the time of menopause. As part of evaluating this association, we will also explore other patterns of OC use, such as early use and long-term use, and other factors associated with this fracture outcome. Cases and controls (n=3,400) will be recruited from a defined population of health maintenance organization enrollees. Cases (n=1,700) will be women 45-59 years of age who are diagnosed with incident physician adjudicated fractures at selected anatomic sites. Controls will be an equal number of age-similar women without fracture, selected randomly from the health plan enrollment databases. Data will be obtained from cases and controls via a standardized telephone-administered interview. Participants will be surveyed regarding types and patterns of OC use during later reproductive life;other OC use and hormonal exposures;and other risk factors for fracture. Computerized pharmacy data are available from 1977 forward as an additional source of OC and medication exposure. Analyses comparing cases and controls with respect to perimenopausal OC use, recency, duration, and other patterns of OC exposure will be conducted to address the study aim. Musculoskeletal disease is the major cause of disability in older persons. Even small changes in the rate of fractures have important public health implications. OC use during middle age is a modifiable factor and this research is important to defining the risks or benefits of these medications. PUBLIC HEALTH RELEVANCE: Fracture rates are of great public health concern and disproportionately affect women after the hormonal changes accompanying menopause. The widespread use of oral contraceptives (OCs) by U.S. women makes understanding the possible effects of this hormonal exposure on fracture risk critical, particularly effects of use close to menopause and use of current types of OCs. Even a small increase or decrease in fracture resulting from OC use could have important implications for clinical practice and for the public health burden of fracture in women transitioning through menopause and beyond.